A family of viruses, characterized as round, non-enveloped virions with mean diameters from 17 to 23.5 nm containing circular, single-stranded deoxyribonucleic acid (ssDNA), has been named the Circoviridae, more commonly referred to as circoviruses. Six viruses have been identified as members of the family, according to The Sixth Report of the International Committee for the Taxonomy of Viruses (Lukert, P. D., G. F. de Boer, J. L. Dale, P. Keese, M. S. McNulty, J. W. Randles, and I. Tisher, 1995, The Circoviridae, pp. 166-168. In F. A. Murphy, C. M. Fauquet, D. H. L. Bishop, S. A. Ghabrial, A. W. Jarvis, G. P. Martelli, M. A. Mayo, and M. D. Summers (eds.), Virus Taxonomy, Sixth Report of the International Committee on Taxonomy of Viruses. Arch. Virol. 10 Suppl.).
Animal viruses included in the family are chicken anemia virus (CAV; the type species), beak and feather disease virus (BFDV; also referred to as psittacine beak and feather disease virus), porcine circovirus (PCV), and pigeon circovirus. Three plant pathogens included as unclassified members of the family are the coconut foliar decay virus (CFDV), banana bunchy top virus (BBTV), and subterranean clover stunt virus (SCSV). All members of the Circoviridae have restricted host ranges. The ssDNA genome of the circoviruses represent the smallest viral DNA replicons known.
DNA sequences have previously been published for the plant viruses, CAV (Notebom, M. H. M., G. F. de Boer, D. J. van Roozelaar, C. Karreman, O. Kranenburg, J. G. Vos, S. H. M. Jeurissen, R. C. Hoeben, A. Zantema, G. Koch, H. van Ormont, and A. J. van der Eb, 1991, Characterization of cloned chicken anemia virus DNA that contains all elements for the infectious replication cycle; J. Virol. 65: 3131-3139) and PCV (Meehan, B. M., J. L. Creelan, M. S. McNulty, and D. Todd, 1997, Sequence of porcine circovirus DNA: affinities with plant circoviruses. J. Gen. Virol. 78:221-227; Buhk, H. J. and A. Mankertz, 1996, Sequence analysis of porcine circovirus; GenBank Accession no. Y0992 1). Analysis of the PCV genome indicates that it possesses an ambisense organization. The viral strand encodes a putative replication-associated protein ("Rep"), herein referred to as ORF V1, with all three sequence motifs found in molecules involved in rolling circle DNA replication, and it possesses the P-loop motif.
PCV was originally isolated in porcine kidney cell cultures and was not considered to be a pathogenic virus. In recent years, the presence of PCV has been linked to a progressive, neurological disorder in pigs, sometimes referred to as "shaky pig syndrome". A circovirus has also been implicated in "postweaning multisystemic wasting syndrome" in swine herds in Canada. Thus, there is a need in the art to develop effective vaccines against porcine circoviruses to control these disorders.
Beak and Feather Disease (BFD) is a debilitating disease that, in its chronic phase, is characterized by feather dystrophy and loss, development of beak deformities and eventual death. Peracute and acute disease caused by the same virus are particularly common in neonatal and young birds, where death can occur within a few weeks, or even days, of the first clinical symptoms. The disease has been described in over 40 species of psittacine birds throughout the world, and new species are being added to the list each year. It is thought that the virus originated in Australian birds and spread to other continents through the worldwide movement of birds to support the companion bird industry. No known cures are available, and while vaccination is considered the best opportunity to prevent infections, no safe and economical vaccine has been available prior to this invention (Ritchie, B W 1995 Avian Viruses: Function and Control, Chapter 8, Wingers Publishing, Inc., Lake Worth, Fla.). Thus, there is a pressing need in the art to develop a vaccine to prevent this debilitating disease, particularly in companion birds.
Circovirus infections in pigeons and doves, members of the Columbiformes, have been linked to disease of the gastrointestinal tract, immune system and feathers which can lead to death (Ritchie, B W 1995, Ibid.)
The present invention addresses these needs for a vaccine against circoviruses by providing nucleic acid and subunit vaccines. Specifically, the nucleic acid sequence of the BFD virus is provided as well as a nucleic acid vaccine comprising BFDV or other circoviral nucleic acids.